Intellectual Property Strategy

On Monday 6 August Novartis
suffered a blow in its battle to obtain Indian patent protection for its beta crystalline form of Glivec (Imatinib mesylate). The case has attracted a lot of attention (a) because of India’s unusual section 3(d) which limits patentability and (b) because this is the first patent to be challenged from the famous mail-box procedure. Although Novartis’ TRIPS challenge looks like a difficult one to win before the WTO, there may be some room to move.

This article provides the background, an update and some strategic options in the dispute and finishes with a list of online resources for further reading. You can comment on this article at the equivalent post on my blog IP ThinkTank.

Background

The patent in issue claims a new crystalline form of imatinib mesylate. The original
composition of matter patent is not patentable in India as it a drug product
patent which was originally filed prior to 1995 when the mail box procedure began.

The Indian Patent Office refused to grant the patent on the ground that it lacked patentability under section 3(d) which states:

‘The following are not inventions within the meaning of this Act,…â€˜the mere discovery of a new form of a known
substance which does not result in the enhancement of the known
efficacy of that substance or the mere discovery of any new property or
new use for a known substance or of the mere use of a known process,
machine or apparatus unless such known process results in a new product
or employs at least one new reactant.’

A brief consideration of the section quickly reveals a few ambiguities (which I won’t discuss here). Section 3(d) was added to the Indian Patent Act as part of the 2005 amendments. The explanation to the amendment states:

‘For the purposes of this clause, salts, esters, ethers, polymorphs,
metabolites, pure form, particle size, isomers, mixtures of isomers,
complexes, combinations and other derivatives of known substance shall
be considered to be the same substance, unless they differ
significantly in properties with regard to efficacy.’

Novartis files two High Court challenges

Novartis’ response to the refusal was to file two High Court Challenges:

(1) – an appeal from the original decision to the Chennai High Court, arguing that the new crystalline form does in fact have an enhanced efficacy as it has a 30% increased bioavailability;

(2) – a challenge to the enactment of section 3(c) on the ground that it was “unconstitutional as it is vague,
arbitrary and violative of Article 14 of the constitution (right to equality).”

(1) – The Appeal

Unfortunately, this has not progressed very far. On 2 April 2007, the Indian Government issued a notification declaring that section 117G of the Indian Patent (Amendment) Act 2005 (which provided that all pending appeals in the High Court shall be transferred to the
Appellate Board set up under the Act), was to be made effective as of 2
April 2007.

Consequently, the Glivec appeal was transferred to the Intellectual Property Appeals Board (IPAB). The IPAB had been running since 2003, but had never heard a patent case as it did not have a ‘technical member’. Former Patent Controller S Chandrasekharan was appointed as the technical member of the newly constituted IPAB for patents.

Novartis appealed Chandrasekharan’s appointment as he had been the presiding Controller at the office which originally refused the patent. To make the perceived conflict worse, before the proceedings were transferred from the High Court, Chandrasekharan had filed an affidavit defending the rejection of the patent application by the patent office.

Curiously, the IPAB itself heard the appeal about its own membership, and unsurprisingly, dismissed the appeal. On 3 August 2007, Novartis appealed this decision at the Chennai High Court.

So, we’re back before the Chennai High Court on a narrow question of the composition of the IPAB. This could take a while, folks.

It seems reasonably clear that the IPAB will be forced to remove Chandrasekharan by the High Court. The same mess has recently occurred, also concerning Chandrasekharan in the Magotteaux
International appeal. (Magotteaux had to go through the same 5-step process – High Court writ, removal to IPAB, challenge to membership, refusal, appeal to High Court.)

Once the membership of the IPAB is sorted out, the real question will be whether the beta crystalline form is patentable within the confines of s3(d) (and the more usual ground of obviousness). In other words, does the beta crystalline form result in the enhancement of the known
efficacy of imatinib free base form (the subject of the 1992 patent), and is it non-obvious in light of that patent?

Novartis will argue that the 30% increase in bioavailability makes it so. However, there’s a semantic argument that bioavailability is not efficacy to start with. Then there’s the question of whether the 30% threshhold is sufficient to be an ‘enhancement’. After that, there’s always the argument that notwithstanding these section 3(d) arguments, it would have been obvious to produce the mesylate and beta crystalliine form with a reasonable expectation that it would improve therapeutic use and most likely bioavailability. (Note here that to succeed, this obviousness argument needs two steps – the first to the mesylate salt and the second to the beta crystalline form.)

The danger posed by the obviousness argument is clear – it makes irrelevant the s3(d) challenge (which will go to the WTO as explained below). Having said that, (and subject to the prior art), one would expect that Novartis will have some pretty good counter arguments – they do this all the time all over the world.

(2) The challenge to section 3(d)

On 6 August, the High Court in Chennai dismissed the writ petition challenging the
constitutionality of Section 3(d), and deferred to the World Trade
Organization (WTO) to resolve the TRIPS compliance question.

It makes sense that the Chennai High Court refused to hear the application. Compliance with TRIPS isn’t a constitutional matter under Indian law.

Having said that, the case has certainly created a lot of publicity about this unusual section of Indian patent law. The ongoing debate is not a bad place to launch a WTO challenge. Strategically then, by running the challenge, Novartis has helped set the stage for the real battle – before the WTO.

“…section 3(d) is compatible with
TRIPS, as it is an “obviousness” standard that member states are free
to define in a manner consistent with their national policy. Section
3(d) does not “discriminate” against the pharmaceutical sector but only
makes a “justified” differentiation, given the specificity of salt
forms in the pharmaceutical sector i.e. other technology sectors such
as mechanicals, electronics etc do not face â€œdifferent salt formâ€ kind
of issues.

It bears
noting that US patent law encompasses a heightened utility requirement
in the context of gene patentsâ€”i.e. in order to be patentable, a gene
sequence has to demonstrate â€œsubstantialâ€, “specific” and “credible”
utility. This came out of a desire to put a stop on the multitude of
frivolous gene patent applications that cited the obvious utility of
being a â€œmere probeâ€. These steps that cater to the specificities of
technology sectors are perfectly legitimate exercises of national
discretion by member states. And India is no different. For
similar reasons, section 3(d) is not likely to be struck down as an
â€œarbitraryâ€ standard under Art 14 of the Constitution of India.”

I tend to agree with Shamnad – at least in relation to patentability of new forms of known substances.

However, section 3(d) also provides a blanket ban from patentability of all new uses of known substances. The difference is that new forms of known substances are subject to the proviso that they are not patentable if they ‘[do] not result in the enhancement of the known
efficacy of that substance‘. This proviso brings Shamnad’s argument into play – that this is merely an obviousness requirement and so is in compliance with TRIPS. (The obviousness analogy is a very good one, and it is quite arguable that the law of many jurisdictions would bar from patentability a very similar set of patents as are barred under India’s s3(d). See for example the anonymous comment on the situation in Europe at the IPKat’s post “Novartis fight for patentability in India“).

However, the ban on new uses of known substances does not have any such proviso. It simply states:

‘The following are not inventions within the meaning of this Act’:

…

(d) … a new use for a known substance…’

I haven’t looked, but I wonder whether there is any disclosure in the patent in issue to enable claims to a new use. If this were the case, perhaps Novartis could win at least on the new use of a known substance limb of the argument. If successful on both, then back India, they could argue that the beta crystalline form is used in a new way (subject to the disclosure in the patent, and an amendment, of course).

(The other ban from section 3(d) is on discoveries of new properties of a known substance. It is well known across the world that mere discoveries themselves are not patentable. Consequently, patent protection would be sought for the new use which becomes possible as a result of the new property.)

Summing Up

In the Appeal, the IPAB will likely be reconstituted without Mr Chandrasekharan. The IPAB will then have to consider patentability and, to win, Novartis must convince the IPAB that (a) in relation to s3(d) the 30% increase in bioavailability is an enhanced efficacy and so the beta crystalline form is patentable, and (b) the beta crystalline form of the mesylate salt is not obvious in light of the free base form.

Whoever wins, there will be an appeal back to the Chennai High Court, and then possibly on to the Supreme Court.

The s 3(d) challenge will take a long time to wind its way through the WTO process. Novartis appear to have a difficult task to win on the argument that the restriction on patentability of new forms is not compliant with TRIPS. However, a challenge to the ban on new uses of known substances may be more successful (though fruitless unless they can obtain claims to a new use).

As I mentioned in my earlier blog post, after all of that, India could still grant a Compulsory License to a generic company. To the best of my knowledge, India has not granted a Compulsory License before – presumably because of the lack of product patents has meant that they did not need to.